Epidermal Growth Factor Receptor is a Predictor of Tumor Response in Locally Advanced Rectal Cancer Patients treated with Preoperative Radiotherapy

Heather Jones, MD
University of Pennsylvania Cancer Center
Last Modified: November 4, 2001

Presenter: J.S. Kim
Affiliation: Radiation Oncology, Hospital Vall d'Hebron, Barcelona, Spain

Background
Epidermal growth factor receptor (EGFR) is a member of the tyrosine kinase receptor family and is expressed in a variety of different cell lines. EGFR overexpression is observed in 50- 70% of colorectal carcinomas and is associated with poor prognosis. However, there are no data on the effect of EGFR overexpression and response to radiochemotherapy in rectal carcinoma. This study evaluated overexpresion of EGFR as a predictor for tumor response in a group of patients with locally advanced rectal cancer treated with preoperative radiotherapy with or without simultaneous chemotherapy and radical surgery.

Materials and Methods

Forty-nine patients with locally advanced rectal cancer were enrolled in this study.
Treatment consisted on preoperative pelvic radiotherapy (total dose 45-50 Gy, 1.8 Gy/d)
Twenty-one had 2 courses of 5-FU and Leucovorin , the first and last week of radiotherapy.
Surgical resection was performed 4 to 8 weeks later. Immunohistochemistry for EGFR was determined in the pre-radiation diagnostic biopsy and in the resected specimens. Immunostaining was performed by EGFR monoclonal antibody (Biogenex, MU 207-UC). Immunohistochemical analysis was evaluated according to the positive tumor cell percentage and the staining intensity.
A score of one to five was assigned according to the percentage of positively stained tumor cells and staining intensity was graded qualitatively.
The percentage and intensity scores were multiplied to produce a weighted score for each specimen.
A score of six or more was chosen to represent positive staining (EGFR +), and a score below six represents negative staining.

Results

Mean age of the cohort was 63.9 years (range: 38-85 years). There were 37 males (75%) and 12 females (25%).
Clinical stage was: T2, 4 patients; T3, 38 patients; T4, 4 patients; N0, 20 patients; N1-2, 29 patients.
Preoperative treatment resulted in partial complete response in 8 patients (16%), downstaging (DS) in 12 patients (25%) and in 29 (49%) non response.
A total of 34/49 tumors showed EGFR + (66%).
EGFR + was observed in 25/29 non response biopsies (86%) but only in 9/20 (45%) of the response patients (p=0.003).
EGFR+ was not associated clinical tumor stage or clinical nodal stage.

Author's Conclusions
Overexpression of EGFR by immunohistochemical detection is an indicator for poor response to preoperative radiotherapy for advanced rectal carcinoma and it may be helpful for determining a subgroup of high-risk patients which could required novel therapeutic modalities such as monoclonal antibodies against EGFR.

Clinical/Scientific Implications
It is always the hope of the treating physician to tailor treatment to and individual patient. Gaining insight into the biology of non responders versus complete responders to chemoradiation can only help overcome the factors that foil our ability to cure these patients; and also help tailor therapy base on tumor biology. Both SWOG and RTOG of recently demonstrated the EGFR is important in both local control and distant control of disease.